Surabhi B Vora1,2, Adam W Brothers3, Alpana Waghmare1,2,4, Janet A Englund1,2,4. 1. Division of Infectious Diseases, Department of Pediatrics, University of Washington, Seattle, WA, USA. 2. Seattle Children's Hospital, Seattle, WA, USA. 3. Department of Pharmacy, Seattle Children's Hospital, Seattle, WA, USA. 4. Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Abstract
BACKGROUND: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for high-risk infants with CMV infection. METHODS: We reviewed medical records of infants ≤6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT). RESULTS: Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups. CONCLUSIONS: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.
BACKGROUND:Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for high-risk infants with CMV infection. METHODS: We reviewed medical records of infants ≤6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT). RESULTS: Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups. CONCLUSIONS: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.